Management Of Pancreatic Cancer Research Articles

The Role of Radio-Frequency and Stereotactic Ablation in the Treatment of Pancreatic Cancer.

Pancreatic adenocarcinoma is a very aggressive tumor with a low overall survival rate. The prognostic and the treatment of this disease are strongly interconnected and highly dependent on the resectability criteria of the tumor, surgical excision being the golden standard. For local advance disease or for unresectable tumors, with or without metastasis we can take into consideration as adjuvant therapy, together with chemotherapy, the radiofrequency ablation or stereotactic ablation radiotherapy of the solid tumor mass. This article is a narrative review that aims to describe these two interventional techniques: radiofrequency ablation and stereotactic ablation radiotherapy. We will discuss the techniques themselves, benefits that they bring and also, about the possible complications that can appear when using them in the management of pancreatic cancer.

Options in First Line Management of Metastatic Pancreatic Cancer and the Determinative Role of ECOG Performance Status

Options in First Line Management of Metastatic Pancreatic Cancer and the Determinative Role of ECOG Performance Status

Utility of circulating tumor DNA for predicting prognosis in the management of resectable pancreatic cancer

Background: The measurement of circulating tumor DNA (ctDNA) has been studied in several malignancies, including metastatic pancreatic cancer, but less is known about its utility in monitoring treatment response and recurrence in resectable pancreatic cancer. Methods: We conducted a systematic review of the literature examining the association of ctDNA with overall survival (OS) and disease-free survival. Results: Five articles met our exclusion criteria. Baseline and/or postoperative ctDNA was found to be associated with decreased OS and recurrence-free survival. Discussion: ctDNA has the potential to be used as a prognostic biomarker and to guide therapy in resectable pancreatic cancer.

Covered self-expandable metallic stent versus plastic stent for preoperative endoscopic biliary drainage in patients with pancreatic cancer: a multi-center retrospective cohort study

Background Expanding indications for neoadjuvant chemotherapy (NAC) for resectable pancreatic cancer prolong the period from diagnosis to surgery. In resectable pancreatic cancer with malignant biliary obstruction (MBO), the biliary drainage method without any biliary events is ideally required to safely perform NAC as planned. Plastic stents (PS) have been traditionally used for preoperative biliary drainage; however, recently, covered self-expandable metallic stents (CSEMS) have emerged as a tool for preoperative biliary drainage. Aims To compare CSEMS with PS for preoperative biliary drainage in the management of resectable pancreatic cancer with MBO. Methods In this multicenter retrospective cohort study, we compared CSEMS with PS for preoperative biliary drainage in patients with pancreatic cancer at three tertiary care centers between 2008 and 2019. Results Of the 120 enrolled patients, 45 underwent CSEMS and 75 underwent PS. No significant difference was observed in the basic characteristics between the groups. The rate of recurrent biliary obstruction (RBO) was significantly lower and the time to RBO was significantly longer in the CSEMS group. In multivariate analysis, CSEMS was an independent factor for a longer RBO. However, pancreatitis and cholecystitis were more common in the CSEMS group. The surgery-related adverse events were not significantly different between the two groups, except for longer surgery time and time to discharge in the CSEMS group. Conclusions CSEMS for preoperative endoscopic biliary drainage in patients with pancreatic cancer reduced RBO, although the risk for pancreatitis or cholecystitis could be increased.

Surgical Management of Non-Metastatic Pancreatic Cancer in the United Kingdom: Results of a Nationwide Survey on Current Practice.

BackgroundIt is presently unclear what clinical pathways are followed for patients with non-metastatic PDAC in specialised centres for pancreatic surgery across the United Kingdom (UK).MethodsBetween August 2019 and August 2020 an electronic survey was conducted aiming at a national cohort of pancreatic surgeons in the UK. Participants replied to a list of standardised questions and clinical vignettes, and data were collected and analysed focusing on management preferences, resectability criteria, and contraindications to surgery.ResultsWithin the study period, 65 pancreatic surgeons from 27 specialist centres in the UK (96%) completed the survey. Multidisciplinary team meetings are utilised universally for the management of patients with PDAC, however, different staging systems for resectability classification are being applied. In borderline resectable PDAC, most surgeons were keen to proceed with surgical exploration post NAT, but differences were noted in preferred chemotherapy regimens. Surgeons from standard volume institutions performed fewer vein resections annually and were more likely to deem patients with locally advanced PDAC as unresectable. Intra-institutional variability in patient management was also present and ranging between 20-80%.ConclusionsSignificant variability in the surgical management of non-metastatic PDAC was identified both on inter- and intra-institutional level.

Neoadjuvant therapy in borderline resectable pancreatic cancer: Outcomes in the era of changing practices and evolving evidence

BackgroundNeoadjuvant therapy (NAT) is increasingly being used in the management of borderline resectable pancreatic cancer (BRPC). We compared the outcomes of patients with BRPC treated either with upfront surgery (UPS) or NAT to assess whether increased use of NAT has helped improve perioperative and long-term outcomes. MethodsProspectively maintained database of 201 consecutive patients with BRPC treated at Tata Memorial Center, India, from 2007–2019 was analyzed. ResultsNAT was offered to 148 patients and 53 were planned for UPS. Progression on NAT was seen in 47 (31.8%) patients. Resection was performed in 103 patients (51.24%). The resection rate was significantly lower after NAT as compared with upfront explorations (42.56% vs 75.47%, P = .00) however, R0 resection rate after NAT was significantly better (74.6% vs 42.5%, P = .001). NAT group showed a significant decrease in the pT stage (P = .004), node positivity (60%–31.7%, P = .005%), and perineural invasion (70%–41.6% P = .026). There was no significant difference in the median overall survival (OS) of patients offered NAT versus UPS on an intention-to-treat basis (15 vs 18 months P = .431). However, OS (22 vs 19 months, P = .205) and disease-free survival (DFS) (16 vs 11 months, P = .135) were higher for resected patients in the NAT group and OS was significantly superior in patients completing the course of treatment (34 vs 22 months, P = .010) ConclusionThe progression rate with NAT in patients with BPRC was 31.8%. NAT was associated with significant pathologic downstaging, improvement in R0 resection rate, and survival in resected patients.

P-P58 The role of PET-CT in the management of pancreatic cancer. A Northern Ireland experience

BackgroundDiagnosis and staging has proven to be difficult in 10-20% of patients with pancreatic cancer. The PET-PANC study found that PET-CT significantly influenced the staging and management of pancreatic cancer and therefore the NICE guidelines now advise PET-CT in all patients who have localised potentially resectable disease. This study aimed to investigate the impact of PET-CT on the management of pancreatic cancer patients in a single tertiary referral centre.MethodsThere were 288 patients with pancreatic cancer discussed at the Northern Ireland Regional Hepatobiliary MDM from January 2020 to March 2021. Of these patients, 176 were deemed to have inoperable disease based on initial CT, 5 had borderline resectable disease, 1 had holding chemotherapy due to COVID restrictions and 57 were excluded from surgical resection for a variety of reasons. These included the patient being unfit for surgery, the patient declining operative intervention and an alternative treatment offered as result of COVID-19 pandemic. Therefore, there were 49 patients with pancreatic adenocarcinoma which the MDT concluded should be considered for surgical resection.ResultsA total of 27 patients who were due to undergo a curative resection had a pre-operative PET-CT scan (55.1%). This demonstrated metastatic disease in 9 cases (33.3%). Four patients who did not have a preoperative PET-CT were found to have metastatic disease at operation (9.7%). This equated to a total metastatic incidence of 26.5% in those who had been initially deemed resectable based on CT scan alone. The time interval from MDM decision to surgery averaged 25.4 days in those who did not have a PET/CT compared to 40.43 days in those who did. This was an average delay of 15.07 days until treatment.ConclusionsThis study demonstrates the important role the PET-CT has in the management of patients with pancreatic cancer. A significant number of patients avoided an unnecessary operation which would have delayed the commencement of chemotherapy. However, there are limitations to PET-CT, demonstrated in the patient with an inconclusive result, who was found to have liver metastases at surgery. The introduction of PET-CT in the staging process does undoubtedly cause delays to surgical resection and a more streamlined pathway needs to be developed to limit the delay to curative treatment.

ImmunoPET of Ovarian and Pancreatic Cancer with AR9.6, a Novel MUC16-Targeted Therapeutic Antibody.

Advances in our understanding of the contribution of aberrant glycosylation to the pro-oncogenic signaling and metastasis of tumor cells have reinvigorated the development of mucin-targeted therapies. Here, we validate the tumor-targeting ability of a novel monoclonal antibody (mAb), AR9.6, that binds MUC16 and abrogates downstream oncogenic signaling to confer a therapeutic response. The in vitro and ex vivo validation of the binding of AR9.6 to MUC16 was achieved via flow cytometry, radioligand binding assay (RBA), and immunohistochemistry (IHC). The in vivo MUC16 targeting of AR9.6 was validated by creating a 89Zr-labeled radioimmunoconjugate of the mAb and utilizing immunoPET and ex vivo biodistribution studies in xenograft models of human ovarian and pancreatic cancer. Flow cytometry, RBA, and IHC revealed that AR9.6 binds to ovarian and pancreatic cancer cells in an MUC16-dependent manner. The in vivo radiopharmacologic profile of 89Zr-labeled AR9.6 in mice bearing ovarian and pancreatic cancer xenografts confirmed the MUC16-dependent tumor targeting by the radioimmunoconjugate. Radioactivity uptake was also observed in the distant lymph nodes (LNs) of mice bearing xenografts with high levels of MUC16 expression (i.e., OVCAR3 and Capan-2). IHC analyses of these PET-positive LNs highlighted the presence of shed antigen as well as necrotic, phagocytized, and actively infiltrating neoplastic cells. The humanization of AR9.6 did not compromise its ability to target MUC16-expressing tumors. The unique therapeutic mechanism of AR9.6 combined with its excellent in vivo tumor targeting makes it a highly promising theranostic agent. huAR9.6 is poised for clinical translation to impact the management of metastatic ovarian and pancreatic cancers.

Study on Motion Management of Pancreatic Cancer Treated by CyberKnife.

PurposeWe investigated the movement characteristics of pancreas and the clinical accuracy of tracking pancreas with the Synchrony Respiratory Tracking System (SRTS) during the CyberKnife treatment. These data provide a clinical data basis for the expansion margins of pancreatic tumor target.Methods and MaterialsForty-two patients with pancreatic cancer treated by CyberKnife were retrospectively studied. The pancreatic displacement calculated from the x-ray images collected during the time interval between two consecutive movements constituted a data set.ResultsThe total mean motion amplitudes and standard deviations of pancreatic tumors in SI, LR, AP, and radial directions were 3.66 ± 1.71 mm, 0.97 ± 0.62 mm, 1.52 ± 1.02 mm, and 1.36 ± 0.49 mm, respectively. The overall mean correlation errors and standard deviations were 0.82 ± 0.46 mm, 0.47 ± 0.33 mm, 0.41 ± 0.24 mm, and 0.98 ± 0.37 mm, respectively. The overall mean prediction errors and standard deviations were 0.57 ± 0.14 mm, 0.62 ± 0.28 mm, 0.39 ± 0.17 mm, and 1.58 ± 0.36 mm, respectively. The correlation errors and prediction errors of pancreatic tumors at different anatomical positions in SI, LR, and AP directions were statistically significant (p < 0.05).ConclusionsThe tumor motion amplitude, the tumor location, and the treatment time are the main factors affecting the tracking accuracy. The pancreatic tumors at different anatomical locations should be treated differently to ensure sufficient dose coverage of the pancreatic target area.

Update on optimal management for pancreatic cancer: expert perspectives from members of the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty

ABSTRACT Introduction Pancreatic cancer remains a challenging malignancy due to the high proportion of patients diagnosed at advanced stages and the limited treatment options. This article discusses recent evidence in the management of both localized and advanced pancreatic cancer and offers an expert opinion on current best practice. Areas covered For patients with localized disease, the evidence for adjuvant chemotherapy is discussed as well as emerging neoadjuvant approaches for resectable, borderline resectable, and locally advanced disease. Advances in metastatic disease are discussed including cytotoxic chemotherapy, targeted therapies, and the role of genomic testing to identify patients with molecular alterations. Reviewed literature included journal publications, abstracts presented at major international oncology meetings, and ongoing clinical trials databases. Expert opinion Pancreatic cancer is a devastating diagnosis and despite recent advances has a very poor prognosis. Only a minority of patients, 20%, are diagnosed with potentially curable disease. The shifting paradigm toward neoadjuvant therapy may improve resectability and survival rates; however, robust evidence is required. Thus far, there has only been limited progress in advanced stage disease. Genomic testing may potentially identify more treatment targets although limited to small subgroups.

Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: Role of the Radiologist and Oncologist in the Era of Precision Medicine.

The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. An adequate staging of pancreatic ductal adenocarcinoma and re-assessment of the tumor after neoadjuvant therapy allows the multidisciplinary team to choose the most appropriate treatment for the patient. This review article discusses advancement in the molecular basis of pancreatic ductal adenocarcinoma, diagnostic tools available for staging and tumor response assessment, and management of resectable or borderline resectable pancreatic cancer.

Quantification of Tumor Location and Growth for Orthotopic Pancreatic Cancer Model Using Bioluminescence Tomography-Guided System

<h3>Purpose/Objective(s)</h3> The developing radio-immunotherapy has cast the use of radiation therapy (RT) into a pivotal role in the management of pancreatic cancer. There is a need to study pancreatic cancer in pre-clinical setting to advance our understanding of the role of RT. The challenge to study abdominal malignancy in vivo is lack of proper imaging guidance. Bioluminescence with its strong imaging contrast has been widely used to monitor tumor growth. We innovated 3D bioluminescence tomography (BLT) to guide irradiation for an orthotopic pancreatic ductal adenocarcinoma (PDAC), and monitor its growth and treatment response. <h3>Materials/Methods</h3> To establish the orthotopic PDAC model, we implanted a fraction of BxPc3-Red-FLuc tumor into the pancreas of a nude mouse. For BLT, mice were subject to multi-spectral and multi-projection bioluminescence imaging (BLI), followed by small animal radiation research platform (SARRP) CBCT imaging. CBCT image was acquired to generate anatomical mesh for BLT reconstruction. We inserted a titanium wire to the center of tumor as the marker to validate the BLT localization accuracy. We will also quantify the accuracy of BLT reconstructed volume with MRI and ex vivo method. Volume-averaged bioluminescent power (BP), related to tumor viability, will also be assessed in comparing with surface BLI and ex vivo method, to determine if it is a proper metric for tumor monitoring and assessment. We will further irradiate the in vivo PDAC volume guided by BLT and demonstrate the application of BLT to longitudinally assess the change of PDAC volume/power in response to treatment. <h3>Results</h3> Our initial result shows 3D BLT can retrieve the orthotopic PDAC location within 1.5 mm accuracy at depth from 3-5 mm, common depth observed in pancreatic study. The BP is observed linearly by 12-fold along the tumor growth 4 weeks after tumor implantation. With BLT, we are able to reconstruct the 3D bioluminescent tumor volume using multiple-projection imaging. <h3>Conclusion</h3> The quantitative BLT system offers unique opportunities for researchers to study important pancreatic tumor in orthotopic setting to quantify its location, growth and response to therapeutic intervention.

A narrative review: has regionalization truly achieved its intended goal in the surgical management of pancreatic cancer?

The purpose of this narrative review is to present the data to date on the volume-outcome association in pancreas cancer surgery and describe the prevalence of and barriers to regionalized pancreas cancer care in western health systems. Numerous studies have demonstrated an association between increasing hospital or surgeon volume and improved patient morbidity and mortality in patients undergoing surgery for pancreas cancer. However, since the initial promotion of minimum volume standards, regionalization has remained difficult to establish. A PubMed literature search for years 1995-2020 was conducted to target original research on the volume-outcome association in pancreas cancer and the prevalence of associated regionalized care systems. Peer reviewed original research studies were selected based on their study design and potential to inform meaningful conclusions from the data. Increasing hospital or surgeon volume is associated with improved short and long-term survival in pancreas cancer patients undergoing surgical resection. Despite the knowledge that increasing hospital and surgeon volume is associated with improved operative mortality and long term survival in pancreas cancer, the majority of patients undergo surgery at low volume hospitals with low volume surgeons. Barriers to regionalization are complex and involve the interaction of many conflicting factors and processes on human, health system, and national levels. Better understanding of the barriers to regionalization in pancreas cancer care is needed before this model of care becomes feasible.

A single microbubble formulation carrying 5-fluorouridine, Irinotecan and oxaliplatin to enable FOLFIRINOX treatment of pancreatic and colon cancer using ultrasound targeted microbubble destruction

FOLFIRINOX and FOLFOXIRI are combination chemotherapy treatments that incorporate the same drug cocktail (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) but exploit an altered dosing regimen when used in the management of pancreatic and colorectal cancer, respectively. Both have proven effective in extending life when used to treat patients with metastatic disease but are accompanied by significant adverse effects. To facilitate improved tumour-targeting of this drug combination, an ultrasound responsive microbubble formulation loaded with 5-fluorouridine, irinotecan and oxaliplatin (FIRINOX MB) was developed and its efficacy tested, together with the non-toxic folinic acid, in preclinical murine models of pancreatic and colorectal cancer. A significant improvement in tumour growth delay was observed in both models following ultrasound targeted microbubble destruction (UTMD) mediated FIRINOX treatment with pancreatic tumours 189% and colorectal tumours 82% smaller at the conclusion of the study when compared to animals treated with a standard dose of FOLFIRINOX. Survival prospects were also improved for animals in the UTMD mediated FIRINOX treatment group with an average survival of 22.17 ± 12.19 days (pancreatic) and 44.40 ± 3.85 days (colorectal) compared to standard FOLFIRINOX treatment (15.83 ± 4.17 days(pancreatic) and 37.50 ± 7.72 days (colon)). Notably, this improved efficacy was achieved using FIRINOX MB that contained 5-fluorouricil, irinotecan and oxaliplatin loadings that were 13.44-fold, 9.19-fold and 1.53-fold lower than used for the standard FOLFIRINOX treatment. These results suggest that UTMD enhances delivery of FIRINOX chemotherapy, making it significantly more effective at a substantially lower dose. In addition, the reduced systemic levels of 5-fluorouracil, irinotecan and oxaliplatin should also make the treatment more tolerable and reduce the adverse effects often associated with this treatment.

Challenges for Better Diagnosis and Management of Pancreatic and Biliary Tract Cancers Focusing on Blood Biomarkers: A Systematic Review.

Simple SummaryPancreatic and biliary tract cancers are malignant tumors that have a very poor prognosis and are resistant to chemotherapy. The later a cancer is detected, the worse the prognosis becomes; therefore, early detection is important. Biomarkers are physiological indices that serve as a guide to indicate the presence or absence of a certain disease, or its progression. The purpose of our research is to summarize previously reported biomarkers for the diagnosis and prognosis of pancreatic and biliary tract cancers. Background: pancreatic cancer (PCa) and biliary tract cancer (BTC) are cancers with a poor prognosis and few effective treatments. One of the reasons for this is late detection. Many researchers are tackling to develop non-invasive biomarkers for cancer, but few are specific for PCa or BTC. In addition, genetic abnormalities occur in cancer tissues, which ultimately affect the expression of various molecules. Therefore, it is important to identify molecules that are altered in PCa and BTC. For this systematic review, a systematic review of Medline and Embase to select biomarker studies of PCa and BTC patients was conducted. Results: after reviewing 72 studies, 79 biomarker candidates were identified, including 22 nucleic acids, 43 proteins, and 14 immune cell types. Of the 72 studies, 61 examined PCa, and 11 examined BTC. Conclusion: PCa and BTC are characterized by nucleic acid, protein, and immune cell profiles that are markedly different from those of healthy subjects. These altered molecules and cell subsets may serve as cancer-specific biomarkers, particularly in blood. Further studies are needed to better understand the diagnosis and prognosis of PCa and BTC.

The role of radiotherapy in locally advanced pancreatic cancer.

At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 35% a locally advanced tumour, non-metastatic but unresectable due to vascular invasion, or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for patients with locally advanced tumours.

Indications to total pancreatectomy for positive neck margin after partial pancreatectomy: a review of a slippery ground.

The extension of a partial pancreatectomy up to total pancreatectomy because of positive neck margin examined at intraoperative frozen section (IFS) analysis is an accepted procedure in modern pancreatic surgery with good accuracy. The goal of this practice is to improve the rate of radical (R0) resection in malignant tumors, mainly pancreatic ductal adenocarcinoma (PDAC), and to completely resect pre-invasive neoplasms such as intraductal papillary mucinous neoplasms (IPMNs). In the setting of IPMNs there is a consensus for pancreatic re-resection when high-grade dysplasia and invasive cancer are present at the neck margin. The presence of denudation is another indication for further resection in IPMNs. The role of IFS analysis in the management of pancreatic cancer is more debated. The presence of a positive intraoperative transection margin can be considered the surrogate of a biologically aggressive disease associated with a poorer prognosis. There are conflicting data regarding possible advantages of pancreatic re-resection up to total pancreatectomy, and the lack of randomized trials comparing different strategies does not offer a definitive answer. The goal of this review is to provide an up-to-date overview of the role IFS analysis of pancreatic margin and of pancreatic re-resection up to total pancreatectomy considering different pancreatic tumors.

Apamin-Conjugated Alendronate Sodium Nanocomplex for Management of Pancreatic Cancer.

Pancreatic cancer has a low survival rate and has limited therapeutic options due to the peculiarity of the tumor tissue. Cancer nanotechnology provides several opportunities to resolve such difficulties as a result of the high surface-to-volume ratio of nanostructures. Peptide-drug nanocomplexes have proved to have immense potential in anticancer activity against pancreatic cancer cells. Thus, in the present study apamin (APA) and alendronate sodium (ALS) were combined to form nanocomplexes (APA-ALS-NC) against pancreatic cancer cells. Optimization of ALS, incubation time, and sonication time in terms of particle size of the nanocomplex was carried out. The optimized formulation was evaluated for anticancer activities in pancreatic cancer cells (PANC-1 cells). A Box-Behnken design using ALS, incubation time, and sonication time as independent factors and particle size as the response was chosen to optimize the APA-ALS-NC formulation. The optimized APA-ALS-NC had a particle size of 161.52 ± 8.4 nm. The evaluation of APA-ALS-NC in PANC-1 cells was carried out using various in vitro tests. The IC50 values were determined by MTT assay and found to be 37.6 ± 1.65, 13.4 ± 0.59, and 1.01 ± 0.04 µg/mL for ALS, APA, and APA-ALS-NC, respectively. The higher cytotoxicity activity of APA-ALS-NC was confirmed from the higher percentage of cells in the necrosis phase (apoptosis study) and the G2-M phase (cell cycle study) compared to that of ALS and APA. While the loss of mitochondrial membrane potential was less for APA-ALS-NC, the levels of IL-1β, TNF-α, caspase-3, ROS, IL-6, and NF-kB showed that APA-ALS-NC can significantly enhance apoptosis and cytotoxicity in PANC-1 cells. Moreover, Bax (10.87 ± 1.36), Bcl-2 (0.27 ± 0.02), and p53 (9.16 ± 1.22) gene expressions confirmed that APA-ALS-NC had a significant apoptotic effect compared to ALS and APA. In summary, the APA-ALS-NC had a more significant cytotoxic effect than ALS and APA. The results of the present study are promising for further evaluation in pre-clinical and clinical trials for arriving at a successful therapeutic strategy against pancreatic cancer.

Use of non-cancer drugs and survival among patients with pancreatic adenocarcinoma: a nationwide registry-based study in Norway

Background The prognosis of pancreatic cancer is poor and new treatment strategies are urgently needed. To identify non-cancer drugs that could be re-purposed for cancer, we investigated the association between the use of selected drugs and cancer-specific mortality in a nationwide cohort of pancreatic cancer patients. Material and methods The study is based on linkage between the Cancer Registry of Norway and the Norwegian Prescription Database, comprising 2614 pancreatic cancer patients diagnosed between 2007 and 2014. We evaluated the association between use at diagnosis of a pre-defined list of non-cancer drugs, including metformin, antihypertensives, and statins, and pancreatic cancer-specific mortality, using Cox regression. Patients were defined as users of a particular drug if it was prescribed before diagnosis, and the prescription covered the date of diagnosis. Results In total, 2096 (80.2%) patients died from pancreatic cancer; median survival was 6 months. Statin users (n = 621) had lower mortality (hazard ratio (HR): 0.86; 95% confidence interval (CI) 0.76–0.97) compared to non-users (n = 1993). This association was more pronounced (P-heterogeneity 0.062) in users of hydrophilic (n = 37, HR: 0.61; 95% CI 0.42–0.90) than lipophilic (n = 587, HR: 0.87; 95% CI 0.78–0.98) statins. An indication for lower mortality (HR: 0.85; 95% CI 0.69–1.05) was observed in users of non-selective beta-blockers (n = 113) compared to non-users (n = 2501). Notably, when compared to users of other antihypertensives (n = 643), users of non-selective beta-blockers (n = 40) had lower mortality (HR 0.67; 95% CI 0.47–0.96). The use of other drugs, including selective beta-blockers and metformin, was not associated with mortality. Conclusion The findings suggest an association between the use of statins and non-selective beta-blockers and reduced pancreatic cancer mortality, and add to the literature supporting the design of randomised clinical trials to evaluate those drugs in the management of pancreatic cancer.

Targeting the Stroma in the Management of Pancreatic Cancer.

Pancreatic cancer (PC) presents extremely aggressive tumours and is associated with poor survival. This is attributed to the unique features of the tumour microenvironment (TME), which is known to create a dense stromal formation and poorly immunogenic condition. In particular, the TME of PC, including the stromal cells and extracellular matrix, plays an essential role in the progression and chemoresistance of PC. Consequently, several promising agents that target key components of the stroma have already been developed and are currently in multiple stages of clinical trials. Therefore, the authors review the latest available evidence on novel stroma-targeting approaches, highlighting the potential impact of the stroma as a key component of the TME in PC.